Diminished β-adrenergic receptor responsiveness and cardiac dilation in hearts of myopathic syrian hamsters (BIO 53.58) are associated with a functional abnormality of the G stimulatory protein

Arthur M. Feldman, Rowena G. Tena, Paul D. Kessler, Harlan F. Weisman, Steven P Schulman, Roger S Blumenthal, Donald G. Jackson, Cornelis Van Dop

Research output: Contribution to journalArticle

Abstract

Previous studies have demonstrated a diminution in the bioactivity of the guanine nucleotidebinding regulatory protein that stimulates adenylyl cyclase (Gs) in hearts of the hypertrophic BIO 14.6 Syrian hamster. In this study, we measured functional activity and immunodetectable levels of Gs in a mutant strain of hamsters (BIO 53.58) that develop a dilated cardiomyopathy. Pathological studies demonstrated that 100-day-old BIO 53.58 hamsters had substantial ventricular dilation when compared with age-matched F1B controls. Additionally, these 100-day-old hamsters demonstrated diminished contractile response to β-adrenergic receptor stimulation. The pathological and hemodynamic changes were associated with defective coupling of Gs to adenylyl cyclase as adenylyl cyclase activation was distinctly decreased in the presence of isoproterenol, fluoride ion, guanine nucleotides, and forskolin. Additionally, the ability of the α-subunit of Gs to reconstitute isoproterenol-stimulated adenylyl cyclase activity in S49 cyc- membranes was reduced approximately 65%. By contrast, cyc- complementation assays did not reveal a difference between the functional activity of Gs in hearts from 30-day-old BIO 53.58 hamsters and F1B controls. Furthermore, β-adrenergic receptor stimulation of adenylyl cyclase in the membranes of the young BIO 53.58 hamsters was not significantly different from controls. The substantial alterations in Gs bioactivity in hearts of the 100-day-old BIO 53.58 hamsters was not associated with alterations in the immunodetectable levels of either αGs or αG1 on Western Blots. These results suggest that G protein changes are associated with ventricular dilation in BIO 53.58 hamsters and that G protein levels are not always reflective of G protein bioactivity.

Original languageEnglish (US)
Pages (from-to)1341-1352
Number of pages12
JournalCirculation
Volume81
Issue number4
Publication statusPublished - 1990
Externally publishedYes

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Keywords

  • Antisera
  • Heart failure
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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